Tumorigenesis is fueled in part by an accumulation of genetic and epigenetic (e.g. aberrant methylation of CpG islands) alterations that inactivate tumor suppressor genes. However, it has not been possible to understand the interaction of these mechanisms on a genome-wide scale, since whole-genome methylation profiling has not been amenable to alignment with chromosomal deletion maps. The genesis of low-grade brain tumors (WHO grade II astrocytomas) is accompanied by widespread aberrant CpG island methylation and a relatively small number of deletions, whereas in tumors that have progressed to malignant high-grade astrocytoma (WHO Grades Ill, IV), large deletions are commonplace. We hypothesize that methylation and deletion converge on particular genes during gliomagenesis, and that this convergence in low-grade tumors negatively impacts patient survival. To determine the independent and potentially convergent effects of these mechanisms on tumorigenesis and patient survival, we will; 1) generate whole-chromosome maps of potential methylation sites (CpGs within CpG islands); 2) identify chromosomal regions that are deleted in low and high-grade tumors, and align these with the maps of potentially methylated sites; 3) identify the loci where deletion and aberrant CpG island methylation converge, particularly those present in a proportion of both low and high-grade tumors and; 4) determine if the length of survival of low-grade astrocytoma patients can be predicted from the patterns of aberrant methylation and deletion. By understanding where and when methylation and deletion interact, we will gain a more complete understanding of tumorigenesis in general, and hope to devise an objective guide for improving the therapy and therapeutic decisions for low-grade astrocytoma patients.